Gastrointestinal Drugs

1. Gastrointestinal Drugs

2. Acid-Controlling Agents

3. Acid-Related Pathophysiology The stomach secretes: • Hydrochloric acid (HCl) • Bicarbonate • Pepsinogen • Intrinsic factor • Mucus • Prostaglandins

4. Glands of the Stomach • Cardiac • Pyloric • Gastric • The cells of the gastric gland are the largest in number and of primary importance when discussing acid control

5. Cells of the Gastric Gland Parietal cells • Produce and secrete HCl • Primary site of action for many acid-controller drugs

6. Hydrochloric Acid • Secreted by the parietal cells when stimulated by food • Maintains stomach at pH of 1 to 4 • Secretion also stimulated by: • Large fatty meals • Excessive amounts of alcohol • Emotional stress

7. Cells of the Gastric Gland (cont'd) • Chief cells • Secrete pepsinogen, a proenzyme • Pepsinogen becomes pepsin when activated by exposure to acid • Pepsin breaks down proteins (photolytic) • Mucoid cells • Mucus-secreting cells (surface epithelial cells) • Provide a protective mucous coat • Protect against self-digestion by HCl

9. Acid-Related Diseases • Caused by imbalance of the three cells of the gastric gland and their secretions • Most common: hyperacidity • Clients report symptoms of overproduction of HCl by the parietal cells as indigestion, sour stomach, heartburn, acid stomach

10. PUD: peptic ulcer disease • GERD: gastro esophageal reflux disease • Helicobacter pylori (H. pylori) • Bacterium found in GI tract of 90% of patients with duodenal ulcers, and 70% of those with gastric ulcers • Combination therapy is used most often to eradicate H. pylori

11. Treatment for H. pylori • Eight regimens approved by the FDA • H. pylori is not associated with acute perforating ulcers • It is suggested that factors other than the presence of H. pylori lead to ulceration

12. Types of Acid-Controlling Agents • Antacids • H2 antagonists • Proton pump inhibitors

13. Antacids: Mechanism of Action • Promote gastric mucosal defense mechanisms • Secretion of: • Mucus: protective barrier against HCl • Bicarbonate: helps buffer acidic properties of HCl • Prostaglandins: prevent activation of proton pump which results in  HCl production • Antacids DO NOT prevent the over-production of acid • Antacids DO neutralize the acid once it’s in the stomach

14. Antacids: Drug Effects • Reduction of pain associated with acid-related disorders • Raising gastric pH from 1.3 to 1.6 neutralizes 50% of the gastric acid • Raising gastric pH 1 point (1.3 to 2.3) neutralizes 90% of the gastric acid • Reducing acidity reduces pain • Used alone or in combination

15. Antacids: Aluminum Salts • Forms: carbonate, hydroxide • Have constipating effects • Often used with magnesium to counteract constipation • Examples • Aluminum carbonate: Basaljel • Hydroxide salt: AlternaGEL • Combination products (aluminum and magnesium): Gaviscon, Maalox, Mylanta, Di-Gel

16. Antacids: Magnesium Salts • Forms: carbonate, hydroxide, oxide, trisilicate • Commonly cause diarrhea; usually used with other agents to counteract this effect • Dangerous when used with renal failure —the failing kidney cannot excrete extra magnesium, resulting in hypomagnesaemia • Examples • Hydroxide salt: magnesium hydroxide (MOM) • Carbonate salt: Gaviscon (also a combination product) • Combination products such as Maalox, Mylanta (aluminum and magnesium)

17. Antacids: Calcium Salts • Forms: many, but carbonate is most common • May cause constipation • Their use may result in kidney stones • Long duration of acid action may cause increased gastric acid secretion (hyperacidity rebound) • Often advertised as an extra source of dietary calcium • Example: Tums (calcium carbonate)

18. Antacids: Sodium Bicarbonate • Highly soluble • Buffers the acidic properties of HCl • Quick onset, but short duration • May cause metabolic alkalosis • Sodium content may cause problems in patients with HF, hypertension, or renal insufficiency (fluid retention)

19. Antacids and Antiflatulents • Antiflatulents: used to relieve the painful symptoms associated with gas • Several agents are used to bind or alter intestinal gas and are often added to antacid combination products OTC antiflatulents • Activated charcoal • Simethicone • Alters elasticity of mucus-coated bubbles, causing them to break • Used often, but there are limited data to support effectiveness

20. Antacids: Side Effects Minimal, and depend on the compound used • Aluminum and calcium • Constipation • Magnesium • Diarrhea • Calcium carbonate • Produces gas and belching; often combined with simethicone

21. Antacids: Drug Interactions • Adsorption of other drugs to antacids • Reduces the ability of the other drug to be absorbed into the body • Chelation • Chemical binding, or inactivation, of another drug • Produces insoluble complexes • Result: reduced drug absorption

22. Antacids: Nursing Implications • Assess for allergies and preexisting conditions that may restrict the use of antacids, such as: • Fluid imbalances – Renal disease – HF • Pregnancy – GI obstruction • Patients with HF or hypertension should use low-sodium antacids such as Reopen, Maalox, or Mylanta II

23. Antacids: Nursing Implications • Use with caution with other medications due to the many drug interactions • Most medications should be given 1 to 2 hours after giving an antacid • Antacids may cause premature dissolving of enteric-coated medications, resulting in stomach upset

24. Antacids: Nursing Implications • Be sure that chewable tablets are chewed thoroughly, and liquid forms are shaken well before giving • Administer with at least 8 ounces of water to enhance absorption (except for the “rapid dissolve” forms) • Caffeine, alcohol, harsh spices, and black pepper may aggravate the underlying GI condition

25. Antacids: Nursing Implications • Monitor for side effects • Nausea, vomiting, abdominal pain, diarrhea • With calcium-containing products: constipation, acid rebound • Monitor for therapeutic response • Notify heath care provider if symptoms are not relieved

26. Histamine Type 2 (H2) Antagonists H2 Antagonists • Reduce acid secretion • All available OTC in lower dosage forms • Most popular drugs for treatment of acid-related disorders • cimetidine (Tegument) • famotidine (Peptide) • ranitidine (Zantac)

27. H2 Antagonists: Mechanism of Action • Block histamine (H2) at the receptors of acid-producing parietal cells • Production of hydrogen ions is reduced, resulting in decreased production of HCl

28. H2 Antagonists: Indications • GERD • PUD • Erosive esophagi is • Adjunct therapy in control of upper GI bleeding • Pathologic gastric hypersecretory conditions (Bollinger-Ellison syndrome)

29. H2 Antagonists: Side Effects • Overall, less than 3% incidence of side effects • Cimetidine may induce impotence and gynecomastia • May see: • Headaches, lethargy, confusion, diarrhea, urticaria, sweating, flushing, other effects

30. H2 Antagonists: Drug Interactions • Cimetidine (Tag met) • Binds with P-450 microsomal oxidase system in the liver, resulting in inhibited oxidation of many drugs and increased drug levels • All H2 antagonists may inhibit the absorption of drugs that require an acidic GI environment for absorption • SMOKING has been shown to decrease the effectiveness of H2 blockers (increases gastric acid production)

31. H2 Antagonists: Nursing Implications • Assess for allergies and impaired renal or liver function • Use with caution in patients who are confused, disoriented, or elderly (higher incidence of CNS side effects) • Take 1 hour before or after antacids • For intravenous doses, follow administration guidelines

32. Proton Pump Inhibitors

33. Proton Pump • The parietal cells release positive hydrogen ions (protons) during HCl production • This process is called the “proton pump” • H2 blockers and antihistamines do not stop the action of this pump

34. Proton Pump Inhibitors: Mechanism of Action • Irreversibly bind to H+/K+ Atlases enzyme • Result: achlorhydria—ALL gastric acid secretion is blocked

35. Proton Pump Inhibitors: Drug Effect • Total inhibition of gastric acid secretion • lansoprazole (Prevacid) • omeprazole (Propose)* • rabeprazole (Cipher) • pantoprazole (Proton) • esomeprazole (Medium) • The first in this new class of drugs

36. Proton Pump Inhibitors: Indications • GERD maintenance therapy • Erosive esophagi is • Short-term treatment of active duodenal and benign gastric ulcers • Zollinger-Ellison syndrome • Treatment of H. pylori–induced ulcers

37. Proton Pump Inhibitors: Side Effects • Safe for short-term therapy • Incidence low and uncommon

38. Proton Pump Inhibitors: Nursing Implications • Assess for allergies and history of liver disease • pantoprazole (Protonix) is the only proton pump inhibitor available for parenteral administration, and can be used for patients who are unable to take oral medications • May increase serum levels of diazepam, phenytoin, and cause increased chance for bleeding with warfarin

39. Proton Pump Inhibitors: Nursing Implications Instruct the patient taking omeprazole (Prilosec): • It should be taken before meals • The capsule should be swallowed whole, not crushed, opened, or chewed • It may be given with antacids • Emphasize that the treatment will be short term

40. Other Drugs • sucralfate (Carafate) • misoprostol (Cytotec)

41. sucralfate (Carafate) • Cytoprotective agent • Used for stress ulcers, erosions, PUD • Attracted to and binds to the base of ulcers and erosions, forming a protective barrier over these areas • Protects these areas from pepsin, which normally breaks down proteins (making ulcers worse) • Little absorption from the gut • May cause constipation, nausea, and dry mouth • May impair absorption of other drugs, especially tetracycline • Binds with phosphate; may be used in chronic renal failure to reduce phosphate levels • Do not administer with other medications

42. misoprostol (Cytotec) • Synthetic prostaglandin analog • Prostaglandins have cytoprotective activity • Protect gastric mucosa from injury by enhancing local production of mucus or bicarbonate • Promote local cell regeneration • Help to maintain mucosal blood flow • Used for prevention of NSAID-induced gastric ulcers • Doses that are therapeutic enough to treat duodenal ulcers often produce abdominal cramps, diarrhea

43. Antidiarrheals and Laxatives

44. Diarrhea • Abnormal frequent passage of loose stool or • Abnormal passage of stools with increased frequency, fluidity, and weight, or with increased stool water excretion Acute diarrhea • Sudden onset in a previously healthy person • Lasts from 3 days to 2 weeks • Self-limiting • Resolves without squeal

45. Chronic diarrhea • Lasts for more than 3 weeks • Associated with recurring passage of diarrheal stools, fever, loss of appetite, nausea, vomiting, weight loss, and chronic weakness

46. Acute Diarrhea Bacterial Viral Drug induced Nutritional Protozoal Chronic Diarrhea Tumors Diabetes Addison’s disease Hyperthyroidism Irritable bowel syndrome Causes of Diarrhea

47. Antidiarrheals: Mechanism of Action Adsorbents • Coat the walls of the GI tract • Bind to the causative bacteria or toxin, which is then eliminated through the stool • Examples: bismuth subsalicylate (Pepto-Bismol), kaolin-pectin, activated charcoal, attapulgite (Kaopectate)

48. Antidiarrheals: Mechanism of Action Anticholinergics • Decrease intestinal muscle tone and peristalsis of GI tract • Result: slowing the movement of fecal matter through the GI tract • Examples: belladonna alkaloids (Don natal), atropine

49. Antidiarrheals: Mechanism of Action • Intestinal flora modifiers • Bacterial cultures of Lactobacillus organisms work by: • Supplying missing bacteria to the GI tract • Suppressing the growth of diarrhea-causing bacteria • Example: L. acidophilus (Lactinex)

50. Antidiarrheals: Mechanism of Action Opiates • Decrease bowel motility and relieve rectal spasms • Decrease transit time through the bowel, allowing more time for water and electrolytes to be absorbed • Examples: paregoric, opium tincture, codeine, loperamide (Imodium), diphenoxylate (Lomotil)